Kidney stone, one of the oldest known diseases, has plagued humans for centuries, consistently imposing a heavy burden on patients and healthcare systems worldwide due to their high incidence and recurrence rates. Advancements in endoscopy, imaging, genetics, molecular biology and bioinformatics have led to a deeper and more comprehensive understanding of the mechanism behind nephrolithiasis. Kidney stone formation is a complex, multi‐step and long‐term process involving the transformation of stone‐forming salts from free ions into asymptomatic or symptomatic stones influenced by physical, chemical and biological factors. Among the various types of kidney stones observed in clinical practice, calcareous nephrolithiasis is currently the most common and exhibits the most intricate formation mechanism. Extensive research suggests that calcareous nephrolithiasis primarily originates from interstitial subepithelial calcified plaques and/or calcified blockages in the openings of collecting ducts. These calcified plaques and blockages eventually come into contact with urine in the renal pelvis, serving as a nidus for crystal formation and subsequent stone growth. Both pathways of stone formation share similar mechanisms, such as the drive of abnormal urine composition, involvement of oxidative stress and inflammation, and an imbalance of stone inhibitors and promoters. However, they also possess unique characteristics. Hence, this review aims to provide detailed description and present recent discoveries regarding the formation processes of calcareous nephrolithiasis from two distinct birthplaces: renal interstitium and tubule lumen.

中文翻译：

---

了解肾间质和肾小管腔钙质肾结石的形成过程

肾结石是已知最古老的疾病之一，几个世纪以来一直困扰着人类，由于其高发病率和复发率，一直给全世界的患者和医疗系统带来沉重负担。内窥镜检查、影像学、遗传学、分子生物学和生物信息学的进步使人们对肾结石背后的机制有了更深入、更全面的了解。肾结石的形成是一个复杂、多步骤、长期的过程，涉及在物理、化学和生物因素的影响下，形成结石的盐从游离离子转变为无症状或有症状的结石。在临床实践中观察到的各种类型的肾结石中，钙质肾结石是目前最常见且形成机制最复杂的。大量研究表明，钙质肾结石主要源自间质上皮下钙化斑块和/或集合管开口处的钙化堵塞。这些钙化斑块和堵塞物最终会与肾盂中的尿液接触，成为晶体形成和随后结石生长的病灶。两种结石形成途径具有相似的机制，例如尿液成分异常的驱动、氧化应激和炎症的参与以​​及结石抑制剂和促进剂的不平衡。然而，它们也具有独特的特征。因此，本综述旨在提供详细描述并介绍有关钙质肾结石形成过程的最新发现，这些结石来自两个不同的发源地：肾间质和肾小管腔。